In December of last year, the FDA issued its guidance to drugmakers regarding the design and use of clinical pharmacology studies required to support a biosimilar candidate. The final guidance aims to provide more direction on the type and scope of information needed to differentiate a “similar” molecule from one that is considered “highly similar” or “highly similar with fingerprint-like similarity.”

Stacie Ropka, an Intellectual Property attorney from Axinn Veltrop & Harkrider who focuses her practice on biosimilars, shares her insight on this latest guidance and how it might impact the growth of the biosimilar market, as well as remaining hurdles sponsors face in gaining regulatory approval. –KB

Contract Pharma: What are the key takeaways from the final guidance regarding clinical pharmacology studies for biosimilars?

Stacie Ropka: The guidance FDA issued December 2016 is the most comprehensive guidance regarding the role of clinical trials as part of the totality of evidence FDA assesses in determining biosimilarity. The guidance explains the role of clinical trials in the overall determination of biosimilarity and provides some concrete examples. For example, pharmacokinetic (PK) data is required but pharmacodynamic (PD) data may also be required. Due to the mechanism(s) of how biologics exert effects, biomarkers are used to determine PD. The guidance provides several characteristics of what makes a good biomarker. Another example of concrete guidance is when a crossover design is recommended vs. a parallel design and vice versa.

The guidance reiterates that clinical trials are a step in the stepwise approach and that useful data from properly designed preclinical studies will be instructive for designing the clinical trials. Therefore, one would want to have an analysis of the data from the preclinical studies prior to designing clinical trials.

Guidance reaffirms that useful data from properly designed clinical trials can support extrapolation from one indication to others. The guidance also reaffirms that with proper bridging studies a sponsor can use a non-U.S. licensed comparator product in certain studies.

CP: How will the guidance impact drug developers / development process?

SR: It will help them plan the series of studies that will ultimately allow FDA to make a determination of biosimilarity. For instance, the timing of studies (sequential), the study design(s), forecasts for launch dates, and planning the product pipeline. In addition to providing guidance regarding targets to select, it also provides guidance for allocating resources over the timeframe typically required in developing and obtaining approval.

CP:How might the FDA’s guidance impact the growth of the biosimilar market?

SR: The final guidance demonstrates the FDA’s commitment to approving biosimilars and companies interested in entering the biosimilar arena should be encouraged because there is more certainty with what studies are required. This is particularly important for clinical trials, which tend to be the most expensive.

Guidance also serves to highlight the relatively more complicated studies required for obtaining data useful in determining biosimilarity. Companies used to the type of clinical trial data required for small molecule pharmaceuticals under Hatch-Waxman may be unprepared for the types of trials and data required for approval of a biosimilar product.

CP: What biosimilars can we expect to be approved in 2017?

SR: Difficult to say. Given that brand products are continuously coming up on expiration of the four-year data exclusivity (i.e., FDA cannot accept a biosimilar application for review until four years after the date of first licensure of the reference product), one would expect there are some attractive targets and we should see applications being filed in 2017. If the 12-year exclusivity has also expired, there is the opportunity for applications filed in 2017 to be approved by end of year.

SR: Biologics are more complicated than small molecule pharmaceuticals. Even though the FDA has provided guidance regarding the stepwise approach to determining biosimilarity, the data has to point to biosimilarity. Technical expertise in making protein-based pharmaceuticals is the best starting point for overcoming the regulatory hurdles in demonstrating biosimilarity.

For more information visit: FDA’s December 2016 GuidanceStacie Ropka holds a Ph.D. in Microbiology and Immunology. Her practice is focused on IP litigation, due diligence and client counseling with an emphasis on the life sciences, biologics and biologic-based pharmaceuticals.